Human leukocyte antigen A*11:01:CT-RCC-1 peptide complex (HLA-A11:CT-RCC-1)

The HLA-A11:CT-RCC-1 peptide complex is a tumor-specific molecular target presented on the surface of clear cell renal cell carcinoma (ccRCC) cells [1, 4]. It consists of the Human Leukocyte Antigen (HLA) allele A*11:01 presenting a 10-amino acid peptide (sequence: ATFLGSLTWK) derived from the human endogenous retrovirus type E (HERV-E) [1, 5]. In healthy tissues, the HERV-E provirus is epigenetically silenced; however, in ccRCC, the loss of the von Hippel-Lindau (VHL) tumor suppressor leads to the stabilization of HIF-2α, which triggers the selective expression of HERV-E [2, 5]. This unique expression pattern makes the HLA-A11:CT-RCC-1 complex an ideal target for immunotherapy, as it is found in approximately 80% of ccRCC tumors but is absent in normal tissues [6, 8]. Therapeutic approaches, particularly T-cell receptor (TCR) engineered T-cell therapies, are designed to recognize this complex and induce a potent cytotoxic immune response against the cancer cells [2, 3]. Clinical development of these therapies focuses on patients who are HLA-A11 positive and whose tumors express the HERV-E antigen [8, 9].

Other names

HLA-A*11:01/CT-RCC-1 complexHLA-A11/HERV-E.CT-RCC-1CT-RCC-1 peptide-MHC complexHERV-E-derived antigen CT-RCC-1HLA-A11:ATFLGSLTWK complex

T-cell receptor (TCR) mediated recognition of the HLA-A11:CT-RCC-1 complex on tumor cells, triggering the release of perforins and granzymes by engineered T cells to induce apoptosis and selective tumor cell lysis [2, 3].